2023
Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma
Berko E, Witek G, Matkar S, Petrova Z, Wu M, Smith C, Daniels A, Kalna J, Kennedy A, Gostuski I, Casey C, Krytska K, Gerelus M, Pavlick D, Ghazarian S, Park J, Marachelian A, Maris J, Goldsmith K, Radhakrishnan R, Lemmon M, Mossé Y. Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Nature Communications 2023, 14: 2601. PMID: 37147298, PMCID: PMC10163008, DOI: 10.1038/s41467-023-38195-0.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnaplastic Lymphoma KinaseCarcinoma, Non-Small-Cell LungCirculating Tumor DNADrug Resistance, NeoplasmHumansLactams, MacrocyclicLung NeoplasmsMutationNeuroblastomaProtein Kinase InhibitorsConceptsAnaplastic lymphoma kinaseLorlatinib resistanceTumor DNAPhase 1 trialCirculating tumor DNAPre-clinical studiesResistance mechanismsTumor DNA samplesALK mutationsDisease progressionHeterogeneity of tumorsClinical utilityRAS-MAPK pathwayTherapeutic strategiesLymphoma kinasePatientsResistance mutationsNeuroblastomaProgressionTrialsMutationsBiochemical assaysDNA samplesPoint mutationsLorlatinibEfficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations
Grant M, Aredo J, Starrett J, Stockhammer P, van Rosenburgh I, Wurtz A, Piper-Valillo A, Piotrowska Z, Falcon C, Yu H, Aggarwal C, Scholes D, Patil T, Nguyen C, Phadke M, Li F, Neal J, Lemmon M, Walther Z, Politi K, Goldberg S. Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations. Clinical Cancer Research 2023, 29: of1-of8. PMID: 36913537, PMCID: PMC10493186, DOI: 10.1158/1078-0432.ccr-22-3497.Peer-Reviewed Original ResearchMeSH KeywordsAniline CompoundsCarcinoma, Non-Small-Cell LungErbB ReceptorsExonsHumansLung NeoplasmsMutationProtein Kinase InhibitorsRetrospective StudiesSequence DeletionConceptsProgression-free survivalNon-small cell lung cancerInferior progression-free survivalMulticenter retrospective cohortEfficacy of osimertinibMulti-institutional cohortCell lung cancerExon 19 deletion mutationUncommon EGFRRetrospective cohortClinical outcomesClinical efficacyLung cancerOsimertinib efficacyEGFR mutationsPreclinical modelsEx19delPatientsAACR Genie databaseLater linesOsimertinibMutant cohortFirst lineCohortEfficacy
2009
The Juxtamembrane Region of the EGF Receptor Functions as an Activation Domain
Brewer M, Choi SH, Alvarado D, Moravcevic K, Pozzi A, Lemmon MA, Carpenter G. The Juxtamembrane Region of the EGF Receptor Functions as an Activation Domain. Molecular Cell 2009, 34: 641-651. PMID: 19560417, PMCID: PMC2719887, DOI: 10.1016/j.molcel.2009.04.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCarcinoma, Non-Small-Cell LungCell LineCell Transformation, NeoplasticChlorocebus aethiopsCOS CellsCrystallography, X-RayDimerizationErbB ReceptorsHumansMiceModels, MolecularMutagenesis, Site-DirectedMutationNIH 3T3 CellsPhosphorylationProtein Structure, TertiaryTyrosineConceptsEpidermal growth factor receptorActivation domainJuxtamembrane regionJM regionGrowth factor receptorIntracellular juxtamembrane regionEGF receptor functionAlanine-scanning mutagenesisFactor receptorTyrosine kinase activationAsymmetric dimerTyrosine kinase domainAutoinhibitory interactionsKinase domainCellular transformationScanning mutagenesisKinase activationEGFR activationC-lobeXenograft assayCancer mutationsC-terminal 19 residuesCrystallographic approachReceptor functionExtensive contacts